Project Summary/Abstract Detection and removal of colorectal adenomas is the recommended approach to the prevention of colorectal cancers (CRC). In separate studies we reported that water infusion in lieu of air insufflation (water method) provided a significantly higher overall adenoma detection rate (ADR) and proximal diminutive ADR than the usual method of air insufflation used during scope insertion. When indigocarmine was added to the water method, the dye highlighted small colonic lesions and significantly increased the overall ADR compared with historical cohorts examined by the water method alone or the conventional air method, as well as proximal diminutive ADR when compared with the water method alone. This proposal addresses the question of whether the water method (with or without indigocarmine) will result in a significantly higher proximal diminutive ADR compared with the air method alone in a RCT. The primary hypothesis asserts that a higher proportion with at least one proximal diminutive adenoma (ADR) will be found in the group randomized to the water + indigocarmine method compared with those randomized to the water method alone or the air method. Asymptomatic veterans referred for sedated colonoscopy for CRC screening at the Sacramento VAMC will be considered for enrollment. Over a 2.5 year recruitment period a total of 330 consented veterans will be randomized to confirm a 20% (34% - 14%) difference in proximal diminutive ADR in favor of the water group in the water vs. air comparison; and a 30% (64% - 34%) difference in favor of the indigocarmine + water method in the indigocarmine + water vs. water comparison. Consent covers agreement to undergo colonoscopy by the randomized methods, respond to pre- and post-colonoscopy questionnaires and allow the examination to be recorded for data analysis in a de-identified fashion. The PI, experienced in all three methods, will examine all enrolled patients. To ensure quality performance, all groups are expected to maintain the recommended overall ADR of 25% in male subjects and 15% in female subjects. Applicable human subject protection and adverse event monitoring procedures will be followed. Outcome data will be gathered and monitored prospectively and guarded by relevant data security measures. Appropriate evaluation with logistic regression and analysis of variance will be employed. Population studies showed that traditional air colonoscopy failed to eliminate post screening colonoscopy cancers or cancer mortality in the proximal colon. Even diminutive adenomas harbor significant dysplasia. A simple, inexpensive, easy-to-learn method of adding indigocarmine to the water method may increase the yield of proximal diminutive adenomas. A higher ADR may minimize the burden of interval CRC by decreasing missed adenomas. The long term goal is to perform further studies to determine if post screening colonoscopy interval cancers and cancer mortality in the proximal colon can be attenuated among the veteran population by the novel methods.